Synthesis and antibiofilm activity of a second-generation reverse-amide oroidin library: a structure-activity relationship study.
A second-generation library of 2-aminoimidazole-based derivatives incorporating a "reversed amide" (RA) motif in comparison to the marine natural product oroidin were synthesized and subsequently assayed for antibiofilm activity against the medically relevant Gram-negative proteobacteria P. aeruginosa and A. baumannii. Most notably, an in-depth activity profile is reported for the most active subclass of derivatives that bear linear aliphatic chains off the amide bond. Additionally, further structural modifications of the core template, such as removal of the amide bond or substitution with a triazole isostere, resulted in the discovery of analogues with antibiofilm activities that varied with respect to their inhibition and dispersal properties of P. aeruginosa and A. baumannii biofilms.
Ballard
T Eric
TE
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA.
Richards
Justin J
JJ
Wolfe
Amanda L
AL
Melander
Christian
C
D040981:Acinetobacter baumannii / Q000187:drug effects / Q000254:growth & development; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D015195:Drug Design; D007093:Imidazoles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007093:Imidazoles; D011758:Pyrroles; D054852:Small Molecule Libraries; C014973:2-aminoimidazole; C077209:oroidin